X-ray Characterization of Conformational Changes of Human Apo- and Holo-Transferrin

Human serum transferrin (Tf) is a bilobed glycoprotein whose function is to transport iron through receptor‐mediated endocytosis. The mechanism for iron release is pH‐dependent and involves conformational changes in the protein, thus making it an attractive system for possible biomedical application...

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Detalles Bibliográficos
Autores: Campos-Escamilla, Camila, Siliqi, Dritan, González-Ramírez, Luis A., López-Sánchez, Carmen, Gavira Gallardo, J. A., Moreno, Abel
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2021
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/257107
Acceso en línea:http://hdl.handle.net/10261/257107
Access Level:acceso abierto
Palabra clave:Conformation change
Human serum transferrin
PH‐dependence
X‐ray crystallography
Descripción
Sumario:Human serum transferrin (Tf) is a bilobed glycoprotein whose function is to transport iron through receptor‐mediated endocytosis. The mechanism for iron release is pH‐dependent and involves conformational changes in the protein, thus making it an attractive system for possible biomedical applications. In this contribution, two powerful X‐ray techniques, namely Macromolecular X‐ray Crystallography (MX) and Small Angle X‐ray Scattering (SAXS), were used to study the conformational changes of iron‐free (apo) and iron‐loaded (holo) transferrin in crystal and solution states, respectively, at three different pH values of physiological relevance. A crystallographic model of glycosylated apo‐Tf was obtained at 3.0 Å resolution, which did not resolve further despite many efforts to improve crystal quality. In the solution, apo‐Tf remained mostly globular in all the pH conditions tested; however, the co‐existence of closed, partially open, and open conformations was observed for holo‐Tf, which showed a more elongated and flexible shape overall.